Supplement Regulation: Be Careful What You Wish For

A recurring theme at SBM is the regulation of supplements, and the impact and consequences of the Dietary Supplement Health and Education Act of 1994 (DSHEA). As one of SBM’s international contributors, I thought it might be helpful to look at how the DSHEA stacks up against the equivalent regulations of its neighbor to the north, Canada. Given the multiple calls for overhauls and changes to DSHEA, an international comparison may help focus the discussion around what a more science-based framework could look like.

Briefly, the DSHEA is an amendment to the U.S. Federal Food, Drug and Cosmetic Act that establishes a regulatory framework for dietary supplements. It effectively excludes manufacturers of these products from virtually all regulations that are in place for prescription and over-the-counter drugs. The FDA notes:

DSHEA draws a crude distinction between food and drugs, even defining therapeutic and pharmacologically-active products (e.g., herbs, botanicals, some hormones) to be categorized as foods, and therefore eligible for DSHEA exemptions from the FDA’s drug regulations.

Manufacturers can put virtually any claim on a supplement, without any requirement to provide persuasive clinical evidence, as long as it’s accompanied by the Quack Miranda Warning: “These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.” Disease treatment claims are not permitted, but are typically restated as permissible “structure/function” claims, implying an ability to improve the structure or function of the body only. (Colloidal silver is one example)

There is a lack of regulatory oversight of manufacturing practices.

In multi-chemical products such as herbals, there is no standardization of active ingredient(s), nor are there mandatory purity guarantees.

There are essentially no pre-marketing requirements before selling products. Once available for sale, there is little ability for the FDA to issue cease-sale orders and recalls. Regulators can block the sale of products only after significant problems have been identified (i.e., ephedra)

The regulation of marketing claims is effectively left to the Federal Trade Commission (FTC), which can prosecute manufacturers for fraud.

The Canadian Regulatory Framework

Until several years ago, Canadian natural health products fell into a regulatory grey zone. Products were treated either as drugs, or as foods. Consultation began in the late 1990’s on a new framework to provide regulation and oversight to these products. In 2004, the Natural Health Product (NHP) Regulations, under Canada’s Food and Drugs Act, became a reality. The NHP Regulations cover nutritional supplements, probiotics, traditional Chinese medicine, vitamins, herbal products, and homeopathy – many of the same products that would be considered “dietary supplements” under DSHEA. Rather than fully regulating these products as drugs, or leaving them virtually unregulated, the NHP regulations were a regulatory compromise: implementing manufacturing quality and safety standards, while significantly relaxing the standards for product efficacy claims. The Natural Health Products Directorate is the unit of Health Canada (Canada’s version of the FDA) that administers the NHP Regulations. Health Canada assures Canadians of the following:

Through the Natural Health Products Directorate, Health Canada ensures that all Canadians have ready access to natural health products that are safe, effective and of high quality, while respecting freedom of choice and philosophical and cultural diversity.

Let’s look at the DSHEA through the Canadian regulatory framework lens. Does it set a science-based example?

Lowering the Efficacy Bar

One of the biggest problems with DSHEA is that it facilitates unsubstantiated efficacy claims. While DSHEA doesn’t apply to homeopathy, the NHP regulations do. Health Canada says that regulated products are “effective,” so what’s the evidence standard being applied?

Health Canada’s Evidence for Homeopathic Medicines: Guidance Document states that applications for licenses for homeopathic products must include evidence to support the “safety, efficacy, and quality” of a homeopathic medication. All “homeopathic medicine” must be from substances referred to in homeopathic pharmacopias, such as the Homeopathic Pharmacopeia of the United States (HPUS), or other references.

Under the NHP Regulations, if randomized, double-blind, placebo-controlled trials are not conducted, manufacturers can make efficacy claims based on “traditional uses”, i.e., anecdotal evidence of use and efficacy. The two most common types of traditional use claims are provings, and references to homeopathic materia medica, which are essentially compilations of provings. There is no objective evaluation of efficacy in provings or in materia medica. Health Canada offers a list of 59 references it will accept at “evidence”, with publication dates as old as 1834 — dating back before the germ theory of disease was proposed.

Consider the popular remedy Oscilliococcinum, sold as an influenza treatment. It’s prepared by decapitating a duck, taking 35 grams of its liver and 15 grams of its heart and fermenting it for 40 days. The solution then undergoes serial dilutions (1 part in 100) 200 times in a row, (in homeopathy lexicon, “200C”) and is dried on lactose/sucrose tablets. (Wikipedia notes that that in order to obtain even a single molecule of the original fermented duck, a volume of tablets greater that the mass of the entire universe would need to be consumed.) Consulting Health Canada’s NHP database (Search NPN 80014156 here) Health Canada has registered the product, with the labelled medicinal ingredient as “Extract of the liver and heart of Annas barbariae: 200C” and approved the following recommended use (translated from French):

This is one consequence of Canadian regulation: the efficacy standard has been lowered so far, it’s meaningless. The Canadian regulatory process assigns distinct registration numbers, dosages, and specific “recommended uses” to hundreds of physically indistinguishable brands of sugar pills.

Again, the evidence bar is far lower than a critical appraisal of the evidence would suggest is accurate. The result? Arguably worse than under the DSHEA. Statements based on questionable evidence gain a regulatory stamp of approval.

Manufacturing Oversight

The NHP Directorate establishes manufacturing standards and issues site licenses. Good Manufacturing Practices (GMP) must be followed. Setting aside the labelling accuracy of homeopathic remedies, the licensure should provide consumers and health professionals with more assurance that what is on the label is actually in the product. Health Canada’s FAQs include a question on DSHEA and it states:

In the United States, dietary supplements are considered as food products under the Dietary Supplements Health Education Act (DSHEA) and, as such, claims may not be made about the use of a dietary supplement to diagnose, prevent, mitigate, treat, or cure a specific disease. These products are not subject to mandatory review, approval or quality requirements, including appropriate testing for identity, purity or potency of active ingredients.

However, GMP standards also exist for supplements sold under DSHEA, so it’s not clear if the NHP regulations impose more strict requirements for Canadian products.

Standardization

The NHP Directorate has created a series of monographs about dozens of single-ingredient products which are intended to provide more standardization of product labeling, dosing and constituents. All of this is worthwhile. Unfortunately a quick scan reveals some significant discrepancies between the current state of the evidence and what’s in the monographs. Harriet Hall’s recent SBM post on glucosamine points out there’s little persuasive data to suggest it has any meaningful effects. In contrast, the current Health Canada-approved monograph for glucosamine selectively cites the positive trials, and labels it effective for osteoarthritis pain. So while the Regulations may be supporting improvements in the consistency of the the finished products, the evidence standards may be compromising their real-world utility.

Marketing and Post-Marketing Surveillance

One of most important elements of the NHP regulations is the implementation of pre-marketing registration requirements. That is, only products reviewed and deemed to meet minimal standards of product quality, safety, and the (relaxed) standard for efficacy claims are permitted to be sold. Unfortunately, even after after six years, thousands of products remain unregistered due to a backlog at Health Canada. Until then, these products continue to be sold. Despite the published standards for consumer advertising of natural health products, there seems to be little enforcement of these requirements. As noted by Tom Blackwell in the National Post,

Recent ads, for instance, tout unapproved natural remedies as being able to prevent diabetes, heart and eye disease, treat menopause and Parkinson’s and help melt away excess weight. By contrast, makers of prescription drugs are essentially barred from promoting their products directly to consumers at all.

Federal law says even natural products — considered generally safer — must be approved under the natural health regulatory system before they can publish or air any kind of ad, and even then must stick closely to the claims allowed in the licence. Many companies that are waiting for word on their applications have chosen to ignore that rule, however, while others have not even attempted to get approval, observers say.

This regulatory backlog seems to have complicated the enforcement of marketing claims, and advertising standards for both approved and unapproved products don’t seem to be facing any serious scrutiny. In Canada, the Competition Bureau is the agency most comparable to the FTC, but it doesn’t seem to have the same focus on actively and publicly prosecuting fraudulent claims. While it has on occasion required companies to change their messaging, it’s rare, and only when the company has gone beyond the already over-generous efficacy claims allowed through the regulations. Perhaps this situation will change when the registration backlog is eliminated.

With respect to product withdrawals, the Minister of Health has the authority under the NHP regulations to direct the stop sale of a product or to cancel licenses of products to prevent injury. Licenses can also be suspended for regulation contravention, or if a product does not appear to meet safety criteria. It’s difficult to directly compare the FDA to Health Canada in this regard, as most Canadian warnings echo FDA advisories for products that may or may not be sold in Canada.

A Science-Based Regulatory Framework for Supplements

Given the regulatory approaches of Canada and the USA, what might a science-based framework look like? I see at least four different perspectives towards supplements/NHPs. I’m sure more will emerge in the comments.

Consumers want products that are safe, and labeled accurately. They may consult health professionals, or make their own decisions about whether products are effective.

Science-based health advocates, like the contributors at this blog, argue that that product safety and quality are paramount, and efficacy statements must be based on good science. They argue against a different approval standard for products just because they’re deemed a “supplement.”

Free market advocates, and those that call for health “freedom” question the value of most regulation that inhibits choice, emphasizing personal responsibility over government-legislated consumer protection measures.

Supplement manufacturers generally seek a market where they face as few regulatory restrictions as possible, whether it be safety, efficacy, or quality.

Certainly, there is some common ground here. Many will likely be agreeable to a regulatory framework that give consumer and health professionals assurance that they’re being protected from health fraud and dangerous products. Even free market advocates generally accept that markets operate less effectively when consumers cannot evaluate benefits and consequences (risks). With respect to health “freedom” claims, I question if anyone anyone wants the “freedom” to be sold products that don’t contain what is claimed, or have not been evaluated to be safe. Turning to manufacturers, some may welcome more rigorous regulatory verification of their own quality processes, especially if it helps with market acceptance.

One approach to to a new framework could be to unbundle the various types of supplements and treat each according to the science. Herbal products and botanicals stands out as the most likely to benefit from some elements of the Canadian regulations. Without quality manufacturing and standardization of active ingredients, it is impossible to infer anything about a particular herb. However, with respect to homeopathy, it’s questionable if anyone benefits from the regulation of sugar pills.

The biggest differences in opinion will clearly be the standards for efficacy and safety claims. Supplements/NHPs will rarely be be supported by the rigorous data we require for prescription and over-the-counter drugs. Through the NHP regulation process, Canada effectively eliminated any meaningful efficacy requirements, to accommodate products like homeopathy. Yet if all treatment and efficacy statements are forbidden, the information will emerge elsewhere. It’s an issue that other regulators are grappling with, too. Ben Goldacre, writing in The Guardian, points out the European Union’s process, evaluating health claims for similar products, has rejected 80% of claims submitted for formal approval. Ben’s solution is unorthodox, but one that I’m starting to warm up to:

You’ll never stop companies making these claims. You’ll never stop people enjoying their claims. This game is at least 200 years old. The best solution I can foresee is an EU-mandated bullshit box, where people can say whatever they want about their product, where consumers can join in, but the game at last is clearly labelled.

Conclusion

Canada has implemented a supplement registration and regulation framework with the goal of assuring Canadians that natural health products are safe, effective, and of high quality. While its approach to manufacturing quality is laudable, there are significant shortcomings with respect to product efficacy standards, and the regulation of marketing. The DSHEA at least informs consumers that the labelled statements on supplements haven’t been evaluated by the FDA. In Canada, with approved products, such as homeopathy, recommended use statements have been both evaluated and approved.

Yet if we want to incorporate dietary supplements into science-based practices, consumers and health professionals need quality products, but also objective and transparent evaluations of efficacy. As a health professional that advises consumers on natural health products, I welcome any regulation assures me, and my patients, that what’s on label is actually in the bottle. Without this information, I can’t make evidence-based recommendations. Yet if a regulatory system doesn’t also properly inform consumers about product effectiveness and safety, how can they be expected to make rational decisions about their own health? Canada’s approach offers some lessons, but also some cautions, for those calling for supplement regulation.